Column arrangement

ABSTRACT

A structure for the absorption or desorption of a substance on a bed through which liquid is allowed to pass comprises a vessel containing a liquid-permeable bed, a lower adaptor, an upper adaptor and means for providing a liquid flow to the bed through one of the adaptors and means for conducting a liquid flow away from the bed through the other adaptor. The lower adaptor is arranged in the lower part of the vessel and at least partially defines the vessel bottom. The lower adaptor has an opening for the passage of liquid to or from the lower part of the vessel, which opening is directed toward the bed, and the lower adaptor is provided with a distribution facility for distributing or collecting liquid flow towards or from, respectively, a bottom surface of the bed. The upper adaptor is arranged in an upper part of the vessel and at least partially covers a cross-sectional area of the vessel. The upper adaptor has an opening for the passage of liquid to or from the upper part of the vessel, the opening being directed toward the bed, and the upper adaptor is provided with a distribution facility for distributing or collecting liquid flow towards or from, respectively, an upper surface of the bed.

TECHNICAL FIELD

The present invention relates to a column construction which includes amovable adaptor that can be used to deliver liquid to or to lead liquidaway from a liquid permeable bed in which it is desired to adsorb asubstance present in the incoming liquid. The adaptor may also be usedin the desorption/elution/washing of the bed. The adaptor is adaptedparticularly for fluidized beds (=expanded particle beds).

By "movable" is meant that the adaptor can be moved in the direction offlow applied during an adsorption/desorption/washing process.

A fluidized (expanded) bed consists of particles and a through-flowingliquid that keep the particles suspended within a given volume. Suchbeds have long been used in fermentation processes, among others. Inrecent times the fluidized bed has also been used as a separation mediumin liquid chromatography (WO-A-9218237 and WO-A-9200799).

Particles which have a density which is higher than the density of asurrounding liquid can be fluidized by allowing liquid to flow throughthe bed in a direction which opposes the direction of gravity (anupwardly directed flow). When the particles have a density which islower than the density of the surrounding liquid, a downwardly directedflow is required to fluidize the bed. See WO-A-9218237 and WO-A-9200799.

A fluidized bed is considered to be stable when each individual particlekeeps within a given cross-section of the column (perpendicular to theflow direction). The settling tendencies of the particles (settling ratemeasured without counterflow) depends on density and size. In the caseof a stabilized fluidized bed, this tendency increases continuouslyalong the flow direction. Those particles which have the most pronouncedsettling tendency position themselves furthest down in the column. See,for instance, WO-A-9218237. Stable fluidized beds shall be vertical(±0.5°) with vertical flow direction (±0.5°).

A DESCRIPTION OF THE BACKGROUND ART AND A RESUME OF THE PROBLEMS SOLVEDBY THE INVENTION

Adapters earlier used in liquid chromatography are intended to hold astationary phase (bed) in place and to lead the flow either from or tothe stationary phase. Consequently, adapters have had a distributingfunction on that side which is proximal to the stationary phase, and anopening on the opposite or distal side through which liquid is eitherdelivered or led away.

Movable adapters have earlier been used in chromatography in conjunctionwith matrices which are packed conventionally in columns. Thismovability has been achieved by applying a controllable force on thematrix via the adaptor, either through

a rod which extends up through an upper end-piece on the column; or

a hydraulic/pneumatic pressure applied in the space between the adaptorand an upper end-piece.

This latter alternative also requires the use of a rod which extends upfrom the adaptor through the column end-piece, although in this case inorder to hold the adaptor in position relative to the upper surface ofthe gel bed.

Movable adapters intended for fluidized beds and conventional columnconstructions have long been marketed by Pharmacia Biotech AB, Uppsala,Sweden. These adapters employ hydraulic pressure in accordance with theabove.

The main drawbacks of the known techniques are:

Strict requirements are placed on the sealing surface between columnwall and adaptor, which results in higher manufacturing costs and aleakage sensitive system. The risk of leakage is affected by thetolerances on the column wall and the adaptor seal, sealing pressure andthe resistance of the seal to temperature and chemicals. This has led todemands for extremely small tolerances with regard to the column walland to the adaptor.

The sealing surface between column wall and adaptor makes it difficultto clean the systems. Pockets readily form.

The adaptor jams easily (easily becomes askew) when scaling-up thecolumn (primarily in regard of column diameters larger than 1 m).

The height of the construction is twice that of the height of the column(due to the rod mounted on earlier described movable adapters).

It is difficult to remove air that is able to collect beneath theadaptor (due to the requirement of stationary seals on the earlierdescribed movable adapters).

It is difficult to loosen agglomerated material, cells, bacteria and gelthat may have agglomerated on the bottom surface of the net. Theselayers grow at times and form "cakes" which impede the throughflow ofliquid.

It is necessary to lengthen the net that normally covers that side ofthe adaptor which faces towards the matrix in the case of largerdiameters (>1.5 m), because those nets that are commercially availableare too small.

The invention provides improvements with regard to the aforesaiddrawbacks of known techniques.

DE 1,642,812 describes in FIG. 4 an embodiment of a movable adaptor thatis intended for ion-exchange chromatography on a compact bed. Theadaptor is positioned on top of the bed and is following movements ofthe bed.

BRIEF DESCRIPTION OF THE DRAWINGS

An inventive column construction and adaptor are illustrated in theaccompanying drawings, in which:

FIG. 1a is a side view of one embodiment of an upper adaptor.

FIG. 1b is a view from above of one embodiment of an upper adaptorcomprised of sections. Each small circle represents one section having aflow opening (the centre hole).

FIG. 2 illustrates the inventive construction that was most preferred onthe date from which convention priority is claimed applied forchromatography on a fluidized bed.

FIG. 3 illustrates schematically an inventive construction applied forchromatography on a fluidized bed in which suspended particles have adensity which is higher than the density of the through-flowing liquid.The bed is shown in a non-expanded state prior to chromatography (FIG.3a), in an expanded state (FIG. 3b) and in a collapsed non-expandedstate after chromatography, in which latter state the bed is ready forwashing and/or desorption (FIG. 3c).

FIG. 4 illustrates schematically an inventive construction applied forchromatography on a fluidized bed in which suspended particles have adensity which is lower than the density of the through-flowing liquid.The bed is shown in a non-expanded state prior to chromatography (FIG.4a), in an expanded state (FIG. 4b) and in a collapsed non-expandedstate after chromatography, and ready for washing and/or desorption(FIG. 4c).

Details which have mutually the same function have been identified withthe same reference numerals, unless otherwise stated. The directions ofthe liquid flows are shown with the aid of arrows.

DESCRIPTION OF THE INVENTION

The invention relates to a construction which includes

a. a vessel (1) which contains a liquid-permeable bed (2);

b. a bottom adaptor (3) which (I) is placed in the lower part of thevessel and preferably defines the bottom of the vessel, either totallyor partially, and (II) has an opening (4) through which liquid can bedelivered/led away to/from the lower part of the vessel (preferably thebottom), said opening (4) being also directed preferably towards the bed(2) and provided with a distributing facility (5) fordistribution/collection of liquid flow towards/from the lower part ofthe bed;

c. an upper adaptor (6) which (I) is placed in the upper part of thevessel and preferably covers the cross-sectional area of said vesselcompletely or partially and (II) has an opening (7) through which liquidis able run from/to the upper part of the vessel, said opening (7) alsopreferably being directed towards the bed (2) and provided with adistribution facility (8) for distribution/collection of liquid flowtowards/from the upper part of the bed; and

d. means (23, 24) for leading liquid flow to the adapters (3, 6) throughthe opening (4) in the lower or bottom adaptor (3) and/or through theopening (7) in the upper adaptor (6).

According to the inventive concept, the upper adaptor behaves as abuoyant body when in use. This buoyancy function can be achieved whenthe density of the adaptor is lower than the density of thethrough-flowing liquid, i.e. a density lower than 1 g/cm³ in the case ofwater and water-miscible organic solvents. The adaptor is thus comprisedcompletely or partially of material which has a density below 1 g/cm³.If the adaptor includes material of higher density, this is compensatedfor with cells of lower compactness, e.g. air cells. Because the adaptorbehaves as a buoyant body, it is able to move in the direction of flow(both with and against the flow).

According to the present invention, there can be permitted between theperiphery of the upper adaptor (the buoyant adaptor) and the vessel wallor walls a gap which in normal cases may be 0.01-10 mm in size. This gapprovides the advantage of avoiding "jamming", enables air beneath theadaptor to be easily removed, enables the adaptor to be set into motionin order to release agglomerates that have caked beneath the net,enables desired sensors (e.g. particle sensors) to be inserted into theliquid zone, and so on. An excessively large gap should be avoided,since such a gap may easily result in pockets of liquid in whichmaterial is able to collect in an undesirable manner. The size of anappropriate gap will depend on the inner diameter of the column casing,among other things.

The buoyant adaptor (see FIG. 1a) used in accordance with the inventionhas at least one liquid opening (7) on its upper side. The underside ofthe adaptor is usually circular in shape (faces towards the bed/matrix)and includes a distributing facility (8), which may have the form of onesingle hole or of a number of holes which are distributed uniformlyacross the underside of the adaptor and are in liquid communication withthe opening (7). The distributing facility, or means, may be coveredwith a woven fine-mesh material (net) (9), in order to prevent particlesfrom the matrix/the bed clogging the distributing facility. Asillustrated in FIG. 1b, the adaptor may be comprised of sections (18),each having a liquid inlet/liquid outlet opening (7). The sections neednot abut one another.

Studies made hitherto have indicated that known techniques can beutilized in the construction of the adaptor, provided that therequirements of buoyancy and movability in relation to through-flowingliquid are fulfilled.

The vessel (1) containing the liquid-permeable bed may have any one of anumber of different geometrical shapes, although the most common andmost practical configuration is a generally straight tube (column), i.e.does not taper, which is positioned vertically. The vessel may be madeof glass, plastic, metal or some other inert material.

The liquid-permeable bed is formed by packed beadsor of particles ormonoliths (continuous matrices) . Porous particles and continuousmatrices are often used. Particle beds may be fluidized (=expanded).

The liquid may either flow vertically downwards or vertically upwardswith the tolerances for fluidized beds given above. The precise flowdirection is determined by the design of the distribution facility ineach adaptor. The distributing direction is as a rule the same as forthe openings (7) and (4), respectively.

The devices (23 and 24) used to lead the liquid flow to/from the upperand the lower adaptor are comprised of connections for hoses or pipes,suitably made of plastic, glass, metal, etc. The devices (23 and 24) areonly indicated symbolically in the figures. The flow of liquid isgenerated with the aid of an appropriate pump arrangement connected toone or to both of the adapters by means of said devices (23 and 24).

In order to make possible wider variations in bed height, particledensity, density of through-flowing liquid and flow rate, the upperadaptor (6) may be provided with means which will enable acounterpressure, preferably a controllable counterpressure, to beapplied to the adaptor and therewith counteract the pressure generatedby the through-flowing liquid. This control is preferably effectedpneumatically, by constructing the space (10) above the upper adaptor(6) as a gas chamber (most practically an air chamber) having directconnection to the upper side of the upper adaptor. Such a gas chambercan be created by mounting above the upper adaptor (6) in spacedrelationship therewith an end-piece (11) which sealingly closes theupper end of the vessel. In the case of this embodiment, the opening (7)in the upper adaptor (6) is connected to an outer storage vessel orreservoir (not shown), preferably through the medium of the end-piece(11), by means of a liquid delivery line (12), preferably in the form ofa flexible hose or a flexible pipe of the periscope kind. In theillustrated case, the gas chamber (10) includes an inlet (13) whichcoacts with a valve (14), preferably an adjustable valve for theoutlet/inlet of gas (air). The inlet (13) will normally be arranged onthe end-piece (11). The chamber (10) may be connected controllably to apressure source, preferably via the inlet (13).

In one practical embodiment, the column is provided with a graduatedvertical level pipe (15) which extends parallel with the vessel (thecolumn) and the function of which may be combined with the function of agel-bed sensor or some other sensor (16) relevant to the purpose andfixedly mounted on the adaptor. The sensor may, in turn, be connected toa signal processing unit (17). This arrangement enables the processtaking place in the vessel to be controlled very effectively. Theadaptor can be caused to move with the intention of releasing ordislodging any material that has agglomerated on the adaptor, bypulsating the liquid flow through the column or by pulsating the airpressure in the chamber (10).

FIGS. 3 and 4 illustrate an inventive construction applied to afluidized bed, particularly a stable fluidized bed, in which theparticles have either a higher or a lower density than the density ofthe through-flowing liquid. The vessel (1) has the form of an upstandingcolumn. According to preferred embodiments, the construction includes anair chamber (10) which applies pressure on the upper side of the upperadaptor (6) (the buoyant adaptor) against the through-flowing liquid. Asa result of the flow of liquid through the column, the fluidized bed(primarily a stable bed) can be generated in a zone of the liquidlocated between the upper and the lower adaptor.

When the particles in the fluidized bed have a density which is higherthan the density of the liquid (FIG. 3), the inlet is effected via thelower adaptor (3) and the outlet is effected via the upper adaptor (6),the buoyant adaptor. The reference numeral (20) identifies the bed in anon-expanded state, while reference numeral (21) identifies the bed inan expanded state. When the bed is expanded and adsorption takes place,there will preferably be found a particle-free liquid layer (19) betweenthe upper surface of the expanded bed and the upper adaptor (6, thebuoyant adaptor).

When the density of the fluidized bed particles is lower than thedensity of the liquid (FIG. 4), the inlet is effected via the buoyantadaptor (6) and the outlet is effected via the lower adaptor (3). Thereference numeral (20) identifies the bed in a non-expanded state,whereas the reference numeral (21) shows the bed in an expanded state.When the bed is expanded and adsorption takes place, there willpreferably be found a particle-free liquid layer (19) between the lowersurface of the expanded bed and the bottom adaptor (3).

The described structures may be mounted on a stand provided with feetwhich can be adjusted to facilitate vertical positioning of thestructure. The stand may have the form of at least three stable pullrods which are placed uniformly around and parallel with the walls ofthe vessel (the column). The bottom parts of the rods are bent radiallyoutwards from the vessel (the column), in order to improve stability.

When using the constructions illustrated in FIGS. 3-4, the process iscommenced with a non-expanded bed. The vessel (1) (the column) is filledwith liquid to a predetermined level in a first process stage. Thevessel is filled with liquid which flows in through either the bottom orthe upper adaptor. The direction of the incoming liquid flow isdetermined by whether the particles have a higher or lower density thanthe density of the incoming liquid (see above). The liquid outlet shouldbe closed when filling the vessel, and the valve to the gas chamberopen. When the desired liquid level has been reached, the flow isallowed to continue with the outlet open and the gas chamber closed,optionally after adjusting the rate of flow, until expansion of thefluidized bed is complete, for instance when a stable fluidized bed hasbeen reached. It is normally endeavored to create a matrix-free liquidlayer (19) at a distance of 5-30 mm between the expanded bed and theoutlet adaptor (the upper adaptor in FIG. 3 and the lower adaptor inFIG. 4). This layer impedes clogging of the outlet adaptor. There is norequirement to create a corresponding layer between the inlet adaptorand the fluidized bed. The liquid level in the vessel (column) can belowered, by reducing the liquid flow rate and/or increasing the gaschamber pressure. When the flow rate is increased and/or the gas chamberpressure decreased, a corresponding change in liquid level is obtained.When expansion of the bed is complete, a test run is carried out,optionally subsequent to an intermediate buffer exchange.

Subsequent to adsorption to the matrix, undesired material can be washedaway by passing an appropriate buffer through the bed with the bed fullyexpanded, partially expanded or in a non-expanded state. The extent towhich the bed is expanded can be changed by adjusting the pressureand/or changing the flow rate.

Desorption is effected with a desorption buffer, suitably with the bedin a non-expanded state and with the buffer flowing in a directionopposite to the direction in which adsorption took place. Prior todesorption, the bed is allowed to return to its non-expanded state,whereafter the flow is reversed and adjusted so that a thinparticle-free liquid layer will form between the outlet adaptor (whichis normally used as the inlet adaptor for the desorption process) andthe non-expanded bed.

Washing and desorption may be effected in accordance with FIGS. 3c and4c.

The embodiments illustrated in FIGS. 2, 3 and 4 are the embodiments mostpreferred on the date from which priority is claimed, with theembodiment according to FIG. 3 being the main preference.

I claim:
 1. A structure for the absorption or desorption of a substanceon a bed through which liquid is allowed to pass, the structurecomprising(a) a vessel containing a liquid-permeable bed; (b) a loweradaptor arranged in a lower part of the vessel and at least partiallydefining the vessel bottom, the lower adaptor having an opening for thepassage of liquid to or from the lower part of the vessel, the openingbeing directed towards the bed, the lower adaptor being provided with adistribution facility for distributing or collecting liquid flow towardsor from, respectively, a bottom surface of the bed; (c) an upper adaptorarranged in an upper part of the vessel and at least partially coveringa cross-sectional area of the vessel, the upper adaptor having anopening for the passage of liquid to or from the upper part of thevessel, the opening being directed towards the bed, the upper adaptorbeing provided with a distribution facility for distributing orcollecting liquid flow towards or from, respectively, an upper surfaceof the bed; and (d) means for providing a liquid flow to the bed throughone of the adaptors and means for conducting a liquid flow away from thebed through the other adaptor, wherein the upper adaptor is movablevertically in the vessel and has a density, the density defining meansfor allowing the upper adaptor to float on liquid passing through orcontained in the vessel.
 2. A structure according to claim 1, whereinthe vessel comprises a column casing and the bed is a fluidized bed. 3.The structure of claim 1, wherein the means for providing a liquid flowto the bed is connected with the lower adaptor and the means forconducting a liquid flow away from the bed is connected with the upperadaptor, and further wherein the bed is fluidized with beads having adensity higher than that of a liquid flowing through the bed.
 4. Thestructure of claim 1, wherein the means for providing a liquid flow tothe bed is connected with the upper adaptor and the means for conductinga liquid flow away from the bed is connected with the lower adaptor, andfurther wherein the bed is fluidized with beads having a density lowerthan that of a liquid flowing through the bed.
 5. A structure accordingto claim 1, wherein the upper adaptor has a density lower than 1 g/cm³.6. A structure according to claim 1, wherein the vessel includes meanswhich function to generate a pressure against a liquid in the vessel. 7.A structure according to claim 1, further comprising an end-piecemounted above the upper adaptor, the end-piece sealingly covering thecross-sectional area of the vessel to form a chamber between theend-piece and the upper adaptor.
 8. A structure according to claim 7,wherein the means for conducting a liquid flow away from the bed isconnected with the opening, in the upper adaptor through the end-piece.9. A structure according to claim 7, wherein the means for providing aliquid flow to the bed is connected through the end-piece to the openingin the upper adaptor.
 10. A structure according to claim 7, wherein thechamber is provided with an air inlet.
 11. A structure according toclaim 10, wherein the air inlet is provided in the end-piece.